Elucidating the role of the Adipor1 receptor in a polymicrobial abdominal sepsis mouse model 4382

Abstract Description Sepsis is a life-threatening condition caused by the body’s extreme response to an infection, leading to tissue damage, organ failure, and potentially death. Globally, sepsis is the leading cause of death in children, claiming nearly 3.4 million lives annually. The urgent need for therapies is hindered by its complex pathophysiology and the difficulty in identifying and validating potential targets. Adiponectin is the most abundant adipokine, and it can bind both Adipor1 and Adipor2. When engaged, the main downstream effects of these receptors are the regulation of metabolism and inflammation through the AMP-activated protein kinase (AMPK) and PPAR-? pathways. Our preliminary analysis of leukocytes from pediatric septic patients showed that Adipor1 was upregulated in acute sepsis and was minimally expressed in healthy controls. Additionally, 12 hours after the induction of polymicrobial abdominal sepsis via a Cecal Ligation and Puncture (CLP) surgery, Adipor1 KO mice exhibited a protective phenotype, characterized by better responsiveness and reduced production of IL-1β in both serum and peritoneal fluid. Preliminary scRNAseq data of blood leukocytes from WT and Adipor1 KO mice showed that Adipor1 was predominantly expressed in neutrophils and that Adipor1 KO neutrophils were associated with altered neutrophil migration and degranulation. To better assess Adipor1 role, we performed in vitro experiments to validate these pathways. Funding Sources CHMC Anestheia Foundation Inc Topic Categories Cellular Adhesion, Migration, and Inflammation (CAM)